Hebrew University of Jerusale

Prof. Amiram Goldblum's

School of Pharmacy
Molecular Modeling and Drug Design Group


64621 - Medicinal Chemistry - Drugs & Drug Action - 70 Hours

This course is presented to 3rd year undergraduates in Pharmacy School, and is
Attended also by undergraduates and graduates from the faculties of Medicine and of Life Sciences. The course consists of 5 frontal hours per week during the first semester (70 hours overall). About half of the course is dedicated to general issues of medicinal chemistry and of drugs. It is followed by chapters on proteinase inhibitors, cholinergics and adrenergics.  The aim of this course is to provide students with the ability to analyze molecular structures and consider their character with respect to solubilities, lipophilicities, electronic structure and acidities, blood brain barrier permeability etc.
Attended regularly by some 140-150 students. Written examination, 2.5 hours.


64751 - Molecular Modeling for Drug Design - 42 hours

An elective course of  3 weekly hours alternating between frontal teaching of principles of modeling (7 meetings) and hands on experiments (7 meetings). The principles cover structure, construction, force fields, minimization and simulation techniques (Molecular Dynamics, Monte Carlo and Simulated Annealing, Free Energy Perturbations, Solvation etc.). Open to students from 2nd year onward and to MSc and PhD students.
Attended by some 40-50 students. Written exam and seminar work required.

64889 - INTRODUCTION TO CHEMINFORMATICS AND QSAR MODELING – 28 Hours (BVy Prof. Alexander Tropsha from UNC Chapel Hill, starting week February 14)

(14 frontal + 14 in PC class), during 7 weeks, spring semester 2011

  1. -          Part I. Foundation of Cheminformatics
  2. -          Part II. Basics of QSAR Modeling
  3. -          Part III. Applications of cheminformatics and QSAR modeling.
  4. PART I. FOUNDATIONS OF CHEMINFORMATICS.  structure representation, curation, storage, retrieval, comparison (references for background reading will be provided)
  5. 1.      Week 1 (each week is two lectures): Structure.
  6. a.       Structure representation (SD files, SMILES files, Mol/Mol2 files
  7. b.      Storage and Retrieval of Chemical Structure Information (SciFinder,eMolecules, PubChem, ChemSpider)
  8. c.       Structural errors and structure curation
  9. d.      Conformational search and pharmacophore modeling
  10. 2.      Week 2. Representation.
  11. a.       Chemical descriptors (1D, 2D, 3D, Atom Pairs, fragments, etc) and the concept of the chemistry space
  12. b.      Clustering and chemical similarity diversity: Euclidean distance; Tanimoto coefficient
  13. c.       Similarity Search: pharmacophore based; descriptor based; shape based;
  14. d.      Virtual Screening/Database mining accuracy: enrichment, ROC curves
  15. e.       Chemical library design: targeted and diverse libraries
  16. PART II. BASICS OF QSAR MODELING. Data preparation; model building and validation; application of models for hit identification.
  17. 1        Week 3. Model building
  18. a    History of QSAR modeling and hierarchy of approaches: 1D, 2D, 3D, nD QSAR.
  19. b    Algorithms for model building: linear (LR, MLR, PLS); non-linear (kNN, ANN, SVM, RF).
  20. c.   Model accuracy evaluation (q2, R2, confusion matrix, classification rate).
  21. 2.      Week 4. Model validation and exploitation.
  22. a.         data preparation and QSAR modeling workflow
  23. b.         model validation: internal and external. Y-randomization; n-fold validation; external validation; applicability domains.
  24. c.         Model interpretation: correlation vs. causation
  25. d.         model exploitation: virtual screening; library design; compound design
  26. PART III. Applications of QSAR modeling: drug discovery; material design; chemical biology and bioinformatics.
  27. 1.      Week 5: Applications of QSAR to ligand based drug discovery
  28. a.       Discovery of novel anticonvulsant agents
  29. b.      Discovery of novel anticancer agents
  30. c.       Discovery of novel GPCR ligands: virtual receptorome screening
  31. d.      QSAR and chemical genomics.
  32. 2.      Week 6. QSAR and predictive ADME/Tox modeling
  33. a.       QSAR and regulatory science; QSAR models of chemical toxicity; environmental QSAR modeling.
  34. b.      QSAR modeling of compound transport and membrane permeability
  35. c.       Novel algorithms integrating QSAR modeling and short term biological assays data: chemical structure – in vitro – in vivo data continuum.
  36. 3.      Week 7. Emerging applications of QSAR modeling.
  37. a.       Integration of QSAR modeling and text/network mining: applications to chemical toxicity/adverse reaction modeling/natural product based drug discovery
  38. b.      QSAR and material design. QSAR modeling of nanomaterials.
  39. c.       Cheminformatics approaches to structure based virtual screening. Integration of cheminformatics and bioinformatics: Chemical descriptors of protein-ligand and protein-protein interfaces.
  40. Max. 30 Students, Individual submission of a worked out problem
Last Update : January 19, 2011| Copyright ©, 2009, The Hebrew University of Jerusalem. All Rights Reserved.